{"id":196,"date":"2023-06-25T11:07:16","date_gmt":"2023-06-25T10:07:16","guid":{"rendered":"https:\/\/microregistrar.com\/?p=196"},"modified":"2023-06-25T11:07:16","modified_gmt":"2023-06-25T10:07:16","slug":"tigecycline","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=196","title":{"rendered":"Tigecycline"},"content":{"rendered":"\n

Nature<\/strong>: Glycylcycline, a member of the tetracycline family. Semisynthetic derivative of minocycline.
MW<\/strong>: 585.6<\/p>\n\n\n\n

Mechanism of action<\/strong>:<\/h3>\n\n\n\n

1. Bind to 30S ribosomal subunit and inhibit protein synthesis \u2013 It inhibits the attachment of aminoacyl tRNA to the A site and prevents chain elongation, i.e. block the translation process.
2. Inhibit mitochondrial protein synthesis by binding to 70 S ribosome (parasites).<\/p>\n\n\n\n

Mechanism of resistance<\/strong>:<\/h3>\n\n\n\n

Two major mechanisms of resistance exist \u2013
1. Overexpression of efflux pump \u2013 help to remove tigecycline from the bacterial cell: 
mepA -MATE family of efflux pump \u2013in Staph aureus.
Multidrug efflux pump (AcrAB\/AcrEF\/AdeABC) \u2013 in gram-negative bacteria.
Multdrug efflux pump (MexXY) \u2013 in Pseudomonas
2. Enzymatic modification \u2013 inactivates tigecycline: tetX gene-mediated.<\/p>\n\n\n\n

Caution\/contraindication<\/strong>:<\/h3>\n\n\n\n

1. Avoid in children <18 years of age \u2013 no data, similar adverse effect as tetracycline (bone growth abnormality, tooth discolouration).
2. Dose adjustment in severe hepatic impairment.
3. Avoid in pregnancy.
4. May increase INR when used with warfarin. May increase PT, aPTT.<\/p>\n\n\n\n

PK\/PD<\/strong>:<\/h3>\n\n\n\n

1. Protein binding: 80%
2. Food improves tolerability.
3. Tissue to plasma concentration ratio is high\u2014low concentration in serum.
4. T1\/2 = 37-66hr
5. Route \u2013 IV
6. <\/strong>Excretion: Mainly excreted through the liver. Renal clearance is only <15%.
7. It doesn\u2019t interact with CYP450.<\/p>\n\n\n\n

Adverse effect<\/strong>:<\/h3>\n\n\n\n

GI side effects (nausea, vomiting)- commonest.
Transient increase in ALT, AST, alk phosphatase.
Potential tooth discolouration and inhibition of bone growth if used in children (or pregnancy) \u2013 no data.
Rare: Hyperpigmentation, electrolyte imbalance, dizziness, vaginitis etc.<\/p>\n\n\n\n

Use<\/strong>:<\/h3>\n\n\n\n

Complicated skin and soft tissue infection.
Complicated intraabdominal infection.
MHRA update 2014 \u2013 Use only when other antibiotics are unsuitable<\/a><\/p>\n\n\n\n

Spectrum<\/strong>:<\/h3>\n\n\n\n

Gram-positive:<\/em><\/strong>
MSSA, MRSA, Streptococcus, Enterococcus including VRE, Listeria, Corynebacterium \u2013 Susceptible.<\/em>
Gram-negative:<\/em><\/strong>
Most enterobacterales (except \u2013 Proteus, Providencia, Morganella), Acinetobacter, Stenotrophomonas, Neisseria -Susceptible.<\/em>
Pseudomonas  is resistant,<\/em>
Burkholderia -may be resistant.<\/em>
Proteus, Providencia, Moganella has high MIC\/resistant<\/em>.
Anaerobe:<\/em><\/strong>
Susceptible, including C difficile.<\/em>
Some strains of B fragilis could be resistant.<\/em>
Atypicals bacteria:<\/em><\/strong>
Mycoplasma, Chlamydia -Susceptible,<\/em>
Rapid growing mycobacteria: fortutum, abscessus, chelonae, smegmatis \u2013 Susceptible.<\/em>
Legionella may have high MIC.<\/em><\/p>\n\n\n\n

Tigecycline Guided search<\/strong><\/a><\/p>\n\n\n\n

Tetracycline and Tigecycline \u2013 similarities and difference<\/em><\/h4>\n\n\n\n
    \n
  1. Tigecycline belongs to the tetracycline family; it is a minocycline derivative<\/em><\/li>\n\n\n\n
  2. It attaches to 30S ribosome like tetracycline and prevents protein synthesis; however, it also binds to the ribosomal binding site, and binding is much stronger than tetracycline.<\/em><\/li>\n\n\n\n
  3. It is not affected by ribosomal binding site protection\u00a0 (tetM, tetO mediated), which confers tetracycline resistance.<\/em><\/li>\n<\/ol>\n\n\n\n

    Possible questions:<\/em><\/strong><\/h4>\n\n\n\n
      \n
    • Tigecycline \u2013 SAQ<\/em><\/li>\n\n\n\n
    • Mechanism of action and mechanism of resistance.<\/em><\/li>\n\n\n\n
    • MCQ based on Mechanism of action\/resistance<\/em><\/li>\n\n\n\n
    • Mutations and efflux pumps involved in resistance<\/em><\/li>\n\n\n\n
    • MCQ\/OSPE based on susceptibility profile, esp learn those that are resistant.<\/em><\/li>\n\n\n\n
    • Management of Multi-drug resistant gram-negative bacteria, like NDM-1<\/em><\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"

      Nature: Glycylcycline, a member of the tetracycline family. Semisynthetic derivative of minocycline.MW: 585.6 Mechanism of action: 1. Bind to 30S […]<\/p>\n","protected":false},"author":1,"featured_media":197,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ngg_post_thumbnail":0,"footnotes":""},"categories":[9],"tags":[28,44],"class_list":["post-196","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-antibiotic","tag-antibiotic","tag-tigecycline"],"_links":{"self":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/196","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=196"}],"version-history":[{"count":1,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/196\/revisions"}],"predecessor-version":[{"id":198,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/196\/revisions\/198"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/media\/197"}],"wp:attachment":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=196"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=196"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=196"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}